System Biology (ISA5101)

Preliminary Project

Group 14

g923922 李昀 g925929 何瓊雯

Project (Tryptophan)

Describe their usage. Find the metabolic pathways involved in

the synthesis of the following compound. Find the enzymes and genes involved in

these pathway reactions. Is E. Coli suitable for biosynthesis of the

above chemicals?

Usage of Tryptophan Tryptophan is an amino acid and essential in human nut

rition. It is one of the 20 amino acids in the genetic code (codon UGG), and its symbol is Trp or W.

Molecular formula : C11H12N2O2 Molecular weight : 204.23 Tryptophan is also a precursor for serotonin, a neurotra

nsmitter, and melatonin, a neurohormone. Tryptophan was once found to be a safe and reasonably

effective sleep aid, probably due to its ability to increase brain levels of serotonin (a calming neurotransmitter when present in moderate levels) and/or melatonin (a drowsiness-inducing hormone secreted by the pineal gland in response to darkness or low light levels).

Usage of Tryptophan In particular, tryptophan showed considerable promise

as an antidepressant, alone and as an “augmentor” of antidepressant drugs. Other promising indications included relief of chronic pain and reduction of impulsive, violent, manic, addictive, obsessive, or compulsive behaviors and disorders.

Metabolic Pathways Involved in the Synthesis of Tryptophan Four major pathways are involved in the synthesis of tryp

tophan (glucose as the carbon source): Phosphotransferase System (PTS) Glycolysis Pentose Phosphate Pathway Glycine, serine and threonine metabolism Pyruvate metabolism Citrate cycle (TCA cycle) Phenylalanine, tyrosine and tryptophan biosynthesis

Metabolic Pathways Involved in the Synthesis of Tryptophan

Metabolic Pathways Involved in the Synthesis of Tryptophan

Metabolic Pathways Involved in the Synthesis of Tryptophan

Metabolic Pathways Involved in the Synthesis of Tryptophan

Metabolic Pathways Involved in the Synthesis of Tryptophan

Metabolic Pathways Involved in the Synthesis of Tryptophan

Metabolic Pathways Involved in the Synthesis of Tryptophan

Glucose PTS G6P

PEP PyuG6P-

F6P

FBP

G3P

BPG

3PG

2PG

PEP

PGI

PFK

ALD

G3PDH

PGK

ENO

PGM

DHAPTPI

Pyr

PK

-

+ATP-

ATP -

AcoA

PDHCitrate

OAA

malate

Fumarate

Succinate

isocitrate

Glyoxylate

-

-

ADP +

Tryptophan

Pyr G3P

Ser

PRPP

Chorismate

DAHP

TrpSynth

ChoSynth

6PG Ribu5P

Rib5PXyl5P

E4PSed7P

F6PRu5P R5PI

PGDH

TKaTKb

TA

DAHPS

?

Enzymes and Genes

Enzymes and genes (also CDS) are classified into different categories of major pathways. Also, special notations are made for those involved in more than a single pathway.

Is E. Coli suitable for biosynthesis of Trp? Our answer is YES. But HOW? Flux distributions must first to be specified under certain

condition. Substances exerting negative or positive control also

need to be fully understood and are required to combine with the model of our proposed dynamic system.

How to balance the flow between synthesis and consumption?

Also, side reactions that are leading to biomass synthesis should not be overlooked in order to ensure sufficient growth.